Leuprolide acetate is a synthetic nona-peptide analog of naturally occurring gonadotropin releasing hormone (GnRH or LH-RH). It is used to treat prostatic cancer in adults and in the treatment of children with central precocious puberty. Presently it is available in the market as an aqueous solution (Lupron®) intended for subcutaneous injection and is available in a 2.8 ml multiple-dose vial containing leuprolide acetate (5 mg/ml) and benzyl alcohol as a preservative (9 mg/ml). The daily recommended dose of leuprolide acetate is 1 mg (200 microliter) administered as a single daily subcutaneous injection. The label indicates that adherence to daily drug administration schedules must be accepted for successful therapy. Further, successful basic therapy with leuprolide acetate requires that the patient be administered a suitable dose of leuprolide acetate daily over a period of six months.
The approved product is available as a 14 Day Patient Administration Kit with 14 disposable syringes and 28 alcohol swabs. The package insert of the approved product provides directions to the user that when the drug level gets low, special care needs to be taken to hold the bottle straight up and down and to keep the needle tip in liquid while pulling back on the plunger. In an attempt to try to get every last drop out of the bottle, there is an increased possibility of drawing air into the syringe and getting an incomplete dose and attendant health risks. The level of the dose is accordingly dependent on the user correctly carrying out the enclosed instructions. In principle, leuprolide acetate can be administered only parenterally and not orally. Further administration of a large amount of active substance solution (e.g. up to 0.2 ml in the case of a certain dosage as with Leuprolide acetate) under the skin every day, may be especially difficult to convey to patients, especially children and cancer patients. Children, in particular may exhibit a certain aversion to taking injection by conventional syringes moreover because considerable injection pain is associated with large volume injections. Cancer patients who are already in a state of high level of pain cannot tolerate even a slight increase in the level of pain. Moreover, it is available in 2.8 ml multiple-dose vial with 14 disposable syringes for daily subcutaneous injection of single doses of 1 mg leuprolide acetate in 0.2 ml of solution, over 14 days. Moreover, the prior art involves withdrawal of the drug solution from a separate storage container. It is apparent that the approved Product® has several drawbacks such as patient non-compliance, possibility of error in withdrawing solution from syringes, and aversion about use of needle and syringe. Further, since the dosing regimen involves daily subcutaneous administration, patient compliance may be a particular concern. Therefore, there lies a requirement for an improved leuprolide acetate subcutaneous injection solution and a method of daily administering leuprolide acetate which takes care of the enumerated problems with the known product and provides an improved effective, user friendly leuprolide therapy. The present invention precisely provides an improvement. The improvement avoids the cumbersome kit of the prior art product, Lupron® and can delivery daily subcutaneous injections of single doses of 1 mg leuprolide acetate in a smaller volume of solution to over more than 14 days, preferably upto 28 days while maintaining sterility of the leuprolide acetate solution. An additional advantage of the preferred embodiments of the present invention is that in a single daily dose a lower amount of preservative is delivered. Additionally, the use of a multiple dose pen device allows flexibility in choosing different volumes of injection by the patient himself with ease, without concern about the accuracy in withdrawing volumes which would be otherwise present a major concern in case of the vial type of product for example as available under the brand name of Lupron®.